Sensors are used to monitor biological, biochemical, or pharmaceutical processes. They are used to monitor a wide variety of measurands, such as flow rate, temperature, pressure, or analytical measurands. Analytical measurands are, for example, concentrations or activities of substances contained in the measuring medium to be monitored or variables correlated to them. Sensors are often stored in a process plant for long periods of time before they are commissioned. In pharmaceutical, biological, biochemical, or biotechnological processes, sensors are often sterilized before being used in a process.
Pharmaceutical, biological, biochemical, or biotechnological processes are increasingly being carried out by means of so-called disposable process solutions, e.g., in process plants in single-use technology. Such process plants comprise pipelines or reactors which are provided as disposable containers (otherwise known as disposables or disposable bioreactors, or single use bioreactors or single-use components). Such disposable containers can, for example, be flexible containers, e.g., bags, hoses, or fermenters. Bioreactors or fermenters often have supply and return lines which can, for example, be provided as hoses. Solid pipe sections can also be used in the supply and return lines. All of these disposable containers can be disposed of at the end of a process. In this way, complex cleaning and sterilization processes are avoided. In particular, the use of disposable containers prevents the risk of cross contamination, thereby increasing process reliability.
The processes performed in the disposable containers run in a closed system, i.e., without being connected to the environment outside the disposable containers. Since sterile conditions are often required, the disposable containers must be sterilized before the introduction of the process media. Gamma radiation is often used for this purpose in biochemical, biological, biotechnological, and pharmaceutical applications. Also, while the processes are running in a disposable fermenter or disposable reactor, foreign substances in particular, germs from the environment must be prevented from penetrating the inside of the process vessel, so that the process flow is not impaired or distorted. The same also applies to supply and return lines which terminate in the disposable fermenter or disposable reactor, or lead out of the disposable fermenter or disposable reactor.
In order to monitor or control processes in such disposable process plants it can, as is the case in conventional process plants, be necessary to measure physical or chemical measurands of the media contained in the process vessels. The measurands to be monitored can, for example, be temperature or analytical measurands, such as pH value, cell density, conductivity, optical transmission or absorption, or a concentration or activity of a chemical substance, e.g., of a specific type of ion of a specific element or of a specific compound, such as the content of dissolved oxygen or CO2. In biotechnological processes, important measurands can also be so-called nutrient parameters, such as the glucose, glutamate, or lactose content of the process medium, or metabolic parameters of the microorganisms used in the processes.
At least some of the aforementioned measurands can be measured by means of optical sensors, for example: an absorption, transmission, or scattered light intensity and thus a cell density a turbidity; a concentration of specific chemical compounds present in the process medium; or a spectrometric or photometric sum parameter can be determined by irradiating the measuring medium with measuring radiation and by recording the measuring radiation intensity after interaction with the medium.
As an alternative to or in addition to optical sensors, electrochemical in particular, potentiometric sensors can be used, for example, to determine the pH value or an ion concentration in the process medium. Amperometric sensors for determining the dissolved oxygen content or the CO2 content, and conductivity sensors that work on a conductive or inductive principle, can also be used.
These sensors can be integrated in the wall of a process vessel in which the process medium to be monitored is contained and/or can have a sensing element integrated in the wall of such a process vessel. Often, so-called in-line measuring systems are used to monitor measuring media flowing through pipelines. As a rule, in-line measuring systems have two connections which can, for example, be arranged opposite one another so that the in-line measuring system can be used in a line of a process plant by having the two connections linked to complementary connections in the line.
An in-line measuring system for measuring and monitoring several measurands, which can, for example, be used to monitor measurement parameters of a medium present, or possibly flowing, in a sterile liquid line of a biochemical, biotechnological, or pharmaceutical process, is known, for example, from U.S. Pat. No. 7,973,923. The sterile liquid line can be a process line of a conventional process plant or a process plant in single-use technology.
The in-line measuring system known from U.S. Pat. No. 7,973,923 comprises a flow-through cell with a supply line and a return line which each has a connection for linking to a line with process medium flowing through it, for example, of a process plant. Furthermore, two sensing elements for recording the values of two mutually different measurands, such as pH value, dissolved oxygen content, CO2 content, concentrations of specific ions, conductivity, or temperature, are integrated by means of connections in the wall of the flow-through cell. The sensing elements integrated in the flow-through cell are in contact with the process medium flowing through the flow-through cell directly for recording measured values. Moreover, the flow-through cell has two mountings for a radiation source module and a radiation receiver module. The radiation source module and the radiation receiver module can be inserted opposite each other into the wall of the flow-through cell by fixing them in the mountings. Both modules each have a transparent window for the measuring radiation emitted by the radiation source, so that the radiation emitted by the radiation source encounters the radiation receiver after passing through the flow-through cell and after interaction with the process medium flowing through the flow-through cell. The radiation receiver is equipped to generate and output an electrical signal which is dependent upon the received radiation intensity. The signal is a measure of a third measurand which can be differentiated from the measurands that are recorded by means of the two sensing elements integrated in the flow-through cell. Therefore, by means of the sensing elements integrated in the wall of the flow-through cell and the optical sensor, measured values of three different measurands of process medium flowing through the flow-through cell can be recorded.
Before sensors are commissioned in a biotechnological, biochemical, or biological process plant, in particular of the type described above, the sensor must often be sterilized first, just like all the other components of the process plant. For this purpose, sensors or in-line measuring systems can be integrated in a process vessel of the plant and sterilized together with the vessel.
When the sensors undergo a storage period, as a result of the sterilization, and/or if there is a long period of time between sterilization and commissioning, properties of the sensing elements can change, which can lead to a change in the respective sensory characteristic curve, e.g., to a drift of the zero point. The sensing elements of potentiometric and amperometric sensors frequently comprise membranes that should ideally be stored in a damp atmosphere to ensure that the sensor provides reliable measured values immediately from the point of commissioning.
In addition to this, sterilization by means of gamma radiation, which is required for many biochemical and biotechnological processes, would lead to the destruction of electronic components in the sensors. For this reason, it is recommended, e.g., in DE 10 2011 080 956 A1, that sensors, or sensing elements integrated in flow-through cells, be arranged as analog sensing elements in the wall of disposable containers to be sterilized, and that they only be detachably connected to an electronic unit comprising non-sterilizable components after sterilization, said electronic unit being designed to process the analog measured values provided by the sensing element. The electronic unit can continue to be used after the end of the process and can be connected to a new sterilized disposable sensing element in a different process arrangement. Since the complete measuring chain of the sensor, which comprises the sensing element and the electronic unit, is not available until commissioning, a calibration or adjustment directly prior to commissioning would also be desirable in such cases.
Therefore, in many applications there is a need for an option for storing sensors or sensing elements in a damp atmosphere and for an efficient calibration and/or verification of sensors shortly before or upon commissioning.